Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation.

ABSTRACT: Mitochondrial dynamics play crucial roles in mitophagy-based mitochondrial quality control, but how these pathways are regulated to meet cellular energy demands remains obscure. Using non-transformed human RPE1 cells, we report that upregulation of mitochondrial oxidative phosphorylation alters mitochondrial dynamics to inhibit Parkin-mediated mitophagy. Despite the basal mitophagy rates remaining stable upon the switch to dependence on oxidative phosphorylation, mitochondria resist fragmentation when RPE1 cells are treated with the protonophore carbonyl cyanide m-chlorophenyl hydrazone. Mechanistically, we show that this is because cleavage of the inner membrane fusion factor L-OPA1 is prevented due to the failure to activate the inner membrane protease OMA1 in mitochondria that have a co

SUBMITTER: MacVicar TD 

PROVIDER: S-EPMC4021475 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature